4.
Inflammation
• The inflammatory response results in: Inflammation
• the leakage of fluids into the
extravascular space (edema); • A primary activity of the
• The leakage of macromolecules such inflammatory response is often to
as fibrinogen and formation of an activate neutrophils--and to cause
extravascular matrix (induration); them to migrate from the blood
vasculature to the extravascular
• The migration of cells (primarily tissues.
neutrophils) from the postcapillary
venules to the extravascular space
(extravasation). • The absence of neutrophils is
essentially incompatible with life.
Neutrophils Neutrophils
• Neutrophils are distinct from other
white blood cells, because of the
presence of enzyme containing
granules in the cytoplasm.
• There are about 3 to 6 x 103
neutrophils present per milliliter of
blood.
• Each day 1011 neutrophils are released
into the bloodstream.
Neutrophils Neutrophils
• Some chemoattractants that stimulate neutrophils
• An important element in the • products of the complement system (specifically
C5a),
normal attack of the neutrophil is • formyl-methionyl-leucyl-phenylalanine (FMLP),
chemotaxis because it allows the • antigen-antibody complexes,
phagocytic cell to come into close • bacterially derived factors (LPS),
proximity with the • products from the lymphocyte series (MAF),
Interleukin 8 (IL8),
microorganism, abnormal cell, or
• products of arachadonic acid specifically
necrotic tissue, to allow for cell Leukotriene B4, and
killing and digestion. • Platelet Activating Factor (PAF).
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5.
Neutrophils Neutrophils
• On the surface of the neutrophil plasma • There are two different types of granules
membrane are opsonins which are distinct from one another on the
• such as C3b (a complement component) or basis of enzyme content, morphology, and
• the Fc portion of immunoglobulins. phase in which they emerge during
• When these receptors are engaged by neutrophil maturation.
opsonized bacteria, the membrane • The two types are the azurophilic granules
invaginates and forms a phagosome. and the specific granules.
Azurophilic granules Azurophilic granules
• Some of the enzymes released by the
• Comprise one third of all mature granules azurophilic granule include
and are not synthesized in the later stages • myeloperoxodase (MPO),
of neutrophil maturation.
• elastase,
• They are predominantly microbicidial and
• neutral proteases,
digestive in function with their enzymes
working • lysozyme, and
• several acid hydrolases.
Azurophilic granules
Myeloperoxidase
• Myeloperoxidase: is a abundant granular
enzyme (accounts for 5% of dry weight of
the neutrophil).
• This enzyme combines hydrogen peroxide
with chloride ions to form hypochlorous acie
(HOCl).
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Azurophilic granules Azurophilic granules
• Lysozyme: like MPO is a microbicidial
enzyme.
• Elastase: is a serine protease which • Lysozyme digests debris from cell walls of
specifically hydrolyzes elastin. bacteria that have already been processed
• Elastin is the major component of elastic by other enzymes.
fibers whcih stretch in the walls of blood • Another function of lysozyme is to modulate
vessels, lungs, and ligaments. inflammation by suppressing neutrophil
chemotaxis and oxidative metabolism.
Macrophage
Macrophage
•Macrophages are Phagocytic
• Endothelial cell, •They express Fc Receptors and
• Kupfer cells, receptors for complement
• histiocytes, components
• microglia, •They can fuse to become
• alveolar macrophages, and multinucleated giant cells
• multinucleate phagocytes in the bone •Macrophages can secrete anti-
are called osteoclasts. microbial substances such as
reactive oxygen species, nitric
oxide, and prostaglandins.
Macrophage Macrophage
The scavenger function of
macrophages prevents the
contents of dying cells from
causing damage or inflammation, •Macrophages produce
in fact, macrophages are so cytokines such as: IFN;
effective it is hard to find dead
cells in healthy tissue--even in TNF; IL-1; IL-6;
locations such as the thymus •Chemokines such as IL-8.
where 98% of the cells die
before leaving.
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7.
Macrophage
Adhesion Proteins
• Macrophages serve as antigen The majority of adhesion molecules fall
presenting cells to activate T cells into one of four families;
• Activated T cells secrete cytokines • cadherins.
that activate most or all of the
above functions of macrophages. • integrins,
• Thus, the T cells and macrophages • immunoglobulin superfamily (IgSF),
stimulate each other and this • selectins
greatly amplifies an immune
response.
CADHERINS CADHERINS
• There is strong evidence to suggest
• They play a fundamental role in that cadherins may be involved in
maintaining the integrity of invasion and metastasis of tumor
multicellular structures and cells.
• areimportant in the diapedesis of
• Finally, cadherins may play a role in
intercellular signalling due to the
lymphocytes and neutrophils discovery of kinases regulating
cytoplasmic cadherin phosphorylation.
Adhesion Proteins
INTEGRINS
The majority of adhesion molecules
fall into one of four families;
• cadherins.
• integrins,
• immunoglobulin superfamily (IgSF),
• selectins
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8.
INTEGRINS
Names expressed by bind to INTEGRINS
Important roles: • tumor metastasis,
• platelet • tissue migration
aggregation, during
embryogenesis.
• inflammation, • signalling
• immune pathways,
function, transmitting
• wound healing, signals both into
and out from cells
INTEGRINS INTEGRINS
Lymphocyte function-associated • Expression of the β1 integrins
antigen-1 (LFA-1, CD11a/CD18). increases significantly late in T-cell
activation, and they are thus often
This is thought to be the most called VLA for very late antigen and
important adhesion molecule for play an important part in directing
lymphocyte activation as antibodies armed effector T cells to their target
to LFA-1 effectively inhibit the tissues.
activation of both naive and armed
effector T cells.
INTEGRINS Adhesion Proteins
• Leukocyte adhesion deficiency (LAD) The majority of adhesion molecules
is a rare inherited disorder in which fall into one of four families;
key functions of leukocytes are • cadherins.
impaired, notably the migration of
neutrophils to sites of extravascaular
• integrins,
inflammation • immunoglobulin superfamily (IgSF),
• selectins
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